Formaldehyde, telomer with 1,3-benzenedimethanamine, 1,3-benzenediol and ethenylbenzene

Endpoint summary

Description of key information

The LD50 value for acute oral toxicity is greater than 2000 mg/kg bw in rats.  The LD50 value for acute dermal toxicity is greater than 2000 mg/kg bw in rats.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH
Sandhofer Weg 7
D-97633 Sulzfeld

- Age at study initiation: 34 d
- Weight at study initiation: 172 - 200 g
- Fasting period before study: yes
- Housing: Granulated textured wood (Granulate A2, J Brandenburg, D-49424 Goldenstedt) was used as bedding material for the cages The cages were changed and cleaned twice a week. Periodic analysis of the bedding material for contaminants based on EPA/USA is conducted at least once a year by LUFA-ITL. During the 14-day observation period the animals are kept singly in MAKROLON cages (type Ill) at a room temperature of 22° C ± 3 ° C (maximum range) and a relative humidity of 60% ± 20% (maximum range). The rooms were lit (150 lux at approx 1 50 m room height) and darkened for periods of 12 hours each.
- Diet (e.g. ad libitum): Altromin 1324 (ALTROMIN GmbH, D-32791 Lage/Lippe, composition see Appendix 1) served as food. Feeding was discontinued approx 16 hours before administration, only tap water was then available ad libitum.
Periodic analysis of the food for contaminants based on EPA/USA1 is conducted at least twice a year by LUFA-11-L2 (limitation for contaminants in the diet see Appendix 2).
- Water (e.g. ad libitum):Drinking w ater in bottles was offered ad libitum. Drinking water is examined according to the 'Deutsche Trinkwasserverordnung, Bun¬desgesetzblatt, Jahrgang 1990' by the Hamburger Wasserwerke, D-20539 Hamburg, at least four times a year (limitation for contaminants in the drinking water see Appendix 1).
- Acclimation period: 5 days



IN-LIFE DATES: From: October 7th, 1999 to October 21st, 1999

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

A dose level of 2000 mg/kg bw, at 10 ml per kg bw, was tested in 5 males and 5 females (Limit-test).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after ad¬ministration. All surviving animals were observed. Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals during the study. Individual body weights were recorded before administration of the substance and thereafter in weekly intervals up to the end of the study, and at death. Changes in weight were calculated when survival exceeds one day
At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. From ani¬mals which survive 24 hours or longer a microscopic examination of all organs which showed evident lesions was performed, if necessary. Autopsy and macroscopic in¬spection of animals which died prematurely were carried out as soon as possible after exitus.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

No mortality

Clinical signs:

other: no clinical signs

Gross pathology:

No pathology, no microscopic examinations

Interpretation of results:

GHS criteria not met

Conclusions:

The substance, when administered by gavage in oil to Sprague-Dawley rats (male and female) in a limit test of 2000 mg/kg bw, resulted in no deaths. The LD50 is over 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March-May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals (approx. 12 weeks old)
- Weight at study initiation: +/- 20% of the sex mean
- Housing: Individually housed in labeled Makrolon cages containing sterilized sawdust as bedding material and paper as cage enrichment
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: free access to water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0-22.2
- Humidity (%): 31-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: 15-29 March 2012

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on Day 1.
Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap
water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Dosage preparation: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance. In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 80ºC for a maximum of 31 minutes. The test substance formulation was allowed to cool down to a temperature of maximally 40ºC prior to dosing.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Body weights: days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes

Statistics:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched and/or flat posture, piloerection, chromodacryorrhoea, ptosis, quick breathing and/or hyperthermia were noted in the majority of animals between Days 1 and 10. General erythema, scales, scabs and/or red staining were seen in the treated skin-area

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of HK 128 in Wistar rats was established to exceed 2000 mg/kg bw.
Based on these results: according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, HK 128 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

adequate

Additional information

Justification for selection of acute toxicity – oral endpoint
No deaths at limit dose of 2000 mg/kg bw

Justification for selection of acute toxicity – dermal endpoint
No deaths at 2000 mg/kg bw

Justification for classification or non-classification

The LD50 values for both acute oral toxicity and acute dermal toxicity exceed 2000 mg/kg bw in rats. According to Regulation EU No. 1272/2008, the material is not classified for acute toxicity.